|Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'/cGMP phosphodiesterase 6C/PDE V-C1
|Ref Sequence ID
|Protein Existence Status
|It acts as cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP
|Composed of two alpha' subunits that are associated with 3 smaller proteins of 11, 13, and 15 kDa.Catalyzes the following reaction-3',5'-cyclic GMP + H2O = GMP + H+. Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.Contain a C-terminal isoprenylation motif to bind the prenyl binding protein/δ (PDE6D).The active site of PDE6C shows a very similar selectivity to the rod PDE6 enzyme for inhibition of catalysis by phosphodiesterase inhibitors.
|Prenylation and Methylation,Lipidation
| Site(s) of PTM(s)
| Matched CATH superfamily
|Predicted Disorder Regions
|TM Helix Prediction
|No TM helices
|Significance of PTMs
|PDE6C contains a carboxyl-terminal CaaX sequence motif that is predicted to direct this protein to undergo sequential posttranslational processing. The first step is the addition of a prenyl moiety on the cysteine residue that is four amino acids from the C-terminus. Next, an endoproteolytic cleavage removes the last three amino acid residues and the prenylated cysteine becomes carboxymethylated. All mammalian PDE6C proteins contain a terminal leucine residue within the CaaX motif making it the preferred substrate for geranylgeranyl transferase (GGTase-I). After biosynthesis, prenylated PDE6C dock to the endoplasmic reticulum and is trafficked by vesicular transport to the outer segments.In zebrafish, a mutation in the PDE6C gene results in a developmental progression of retinal degeneration similar to that of the rd1 mouse model (a model for rod photoreceptor degenerative diseases. Mutations in the PDE6C gene that correlate with diseases such as cone dystrophy and achromatopsia. Defective transport of prenylated proteins (including PDE6C) is observed in mice that lack the prenyl binding protein-δ (PrBP/δ; PDE6D) gene, resulting in altered photoreceptor physiology and slowly progressing cone dystrophy.
|1.Cahill KB, Cote RH. Phosphodiesterase 6C, cGMP-specific cone alpha'. AFCS Nat Mol Pages. 2011;2011:A001756. doi: 10.1038/mp.a001756.01. Epub 2011 Jun 3. PMID: 26504430; PMCID: PMC4618378. 2.Li, T. S., Volpp, K., & Applebury, M. L. (1990). Bovine cone photoreceptor cGMP phosphodiesterase structure deduced from a cDNA clone. Proceedings of the National Academy of Sciences of the United States of America, 87(1), 293–297. https://doi.org/10.1073/pnas.87.1.293